Statins are a widely used class of medications that lower cholesterol levels in patients with hyperlipidemia. Recent evidence suggests that statins can also reduce the risk for cerebrovascular and cardiovascular events and may be helpful in diseases of the central nervous system, including ischemic stroke, Alzheimer disease, and multiple sclerosis. Growing evidence suggests that statin drugs may also protect against worsening of OAG, one of the most common causes of blindness worldwide. Basic scientists have identified several mechanisms by which statins may protect against OAG progression-for example, by improving blood flow to the optic nerve as a result of upregulating endothelial nitric oxide synthase, and by enhancing aqueous outflow through the inhibition of Rho kinase activity. Several cohort and case-control studies have demonstrated reduced rates of OAG or disease stabilization among statin users. In preliminary analyses, we analyzed longitudinal data on a group of 524,109 enrollees, aged 60 years or older, with hyperlipidemia in a large, nationwide, managed-care network and found that persons using a statin agent had a significantly reduced risk for developing OAG and for progressing from suspected glaucoma to OAG, compared with persons who were not using statin drugs. The aim of this R34 clinical trial planning grant is to assemble the necessary infrastructure to carry out a large, multicenter, double-masked, RCT to determine whether statins play a protective role against OAG progression in persons with mild or moderate OAG. An RCT demonstrating that statins protect against worsening of glaucoma would have important clinical implications for patient care, as it would provide an evidence basis for protecting patients from disease progression in this potentially blinding disease by using a commonly available medication for a new indication.